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Overrepresentation of IL-17A and IL-22 producing CD8 T cells in lesional skin suggests their involvement in the pathogenesis of psoriasis.

Res PC, Piskin G, de Boer OJ, van der Loos CM, Teeling P, Bos JD, Teunissen MB - PLoS ONE (2010)

Bottom Line: Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin.Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin.Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.c.res@amc.uva.nl

ABSTRACT

Background: Although recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ.

Methodology/principal findings: By spectral imaging analysis of double-stained skin sections we demonstrated that IL-17 was mainly expressed by mast cells and neutrophils and IL-22 by macrophages and dendritic cells. Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin. However, examination of in vitro-activated T cells by flow cytometry revealed that substantial percentages of skin-derived CD4 and CD8 T cells were able to produce IL-17A alone or together with IL-22 (i.e. Th17 and Tc17, respectively) or to produce IL-22 in absence of IL-17A and IFN-γ (i.e. Th22 and Tc22, respectively). Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin. Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

Conclusions/significance: The increased presence of Tc17 and Tc22 cells in lesional psoriatic skin suggests that these types of CD8 T cells play a significant role in the pathogenesis of psoriasis. As part of the skin-derived IL-17A(pos) CD4 and CD8 T clones developed into IL-22 single-producers, this demonstrates plasticity in their cytokine production profile and suggests a developmental relationship between Th17 and Th22 cells and between Tc17 and Tc22 cells.

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IL-17 and IL-22 expression in psoriatic skin.Microscopic detail of lesional psoriatic skin stained for IL-17 (A–D) or IL-22 (E–H) in combination with CD3 (A, B, E), myeloperoxidase (C), tryptase (D, H), CD11c (F), or CD68 (G). Cytokines are visualized in blue and all different cell markers in red. Each set of three small pictures on the right side represents a composite fluorescent-like image in pseudo-colors of the rectangle-marked area and was obtained after unmixing the individual colors red and blue with spectral imaging. Colocalization of red and blue is indicated in yellow. Spectral imaging analysis of this double-stained series of sections clearly shows the presence of an occasional IL-17pos T cell in psoriatic lesions, whereas IL-22pos T cells were absent. The IL-17 expression in psoriatic skin was predominantly confined to neutrophils and mast cells and IL-22 was highly expressed in many dendritic cells and in most macrophages. The figure is representative of the results from three different donors. Examples of double-stained cells are indicated with an arrow and single-stained cells with an arrowhead. Original magnification 200×.
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pone-0014108-g001: IL-17 and IL-22 expression in psoriatic skin.Microscopic detail of lesional psoriatic skin stained for IL-17 (A–D) or IL-22 (E–H) in combination with CD3 (A, B, E), myeloperoxidase (C), tryptase (D, H), CD11c (F), or CD68 (G). Cytokines are visualized in blue and all different cell markers in red. Each set of three small pictures on the right side represents a composite fluorescent-like image in pseudo-colors of the rectangle-marked area and was obtained after unmixing the individual colors red and blue with spectral imaging. Colocalization of red and blue is indicated in yellow. Spectral imaging analysis of this double-stained series of sections clearly shows the presence of an occasional IL-17pos T cell in psoriatic lesions, whereas IL-22pos T cells were absent. The IL-17 expression in psoriatic skin was predominantly confined to neutrophils and mast cells and IL-22 was highly expressed in many dendritic cells and in most macrophages. The figure is representative of the results from three different donors. Examples of double-stained cells are indicated with an arrow and single-stained cells with an arrowhead. Original magnification 200×.

Mentions: In order to determine the presence and distribution of IL-17 producing T cells in situ, we performed double staining on skin sections from lesional psoriatic skin and healthy normal skin. Spectral digital imaging was used for objective determination of colocalization. Whereas clear IL-17pos and CD3pos cells could be observed in lesional psoriatic skin (Figures 1A and 1B), only an occasional T cell appeared to co-express IL-17. Nevertheless, the presence of IL-17pos T cells seemed to be a specific feature of lesional skin, as in sections from normal skin no double stained cells could be detected (data not shown). In order to identify the IL-17pos non-T cells, we performed additional double stainings. We found that the majority of neutrophils (myeloperoxidase positive) and virtually all mast cells (tryptase positive) in psoriatic skin were IL-17pos (Figures 1C and 1D). We could also detect IL-17pos cells in normal skin, which all appeared to be mast cells and not neutrophils (data not shown).


Overrepresentation of IL-17A and IL-22 producing CD8 T cells in lesional skin suggests their involvement in the pathogenesis of psoriasis.

Res PC, Piskin G, de Boer OJ, van der Loos CM, Teeling P, Bos JD, Teunissen MB - PLoS ONE (2010)

IL-17 and IL-22 expression in psoriatic skin.Microscopic detail of lesional psoriatic skin stained for IL-17 (A–D) or IL-22 (E–H) in combination with CD3 (A, B, E), myeloperoxidase (C), tryptase (D, H), CD11c (F), or CD68 (G). Cytokines are visualized in blue and all different cell markers in red. Each set of three small pictures on the right side represents a composite fluorescent-like image in pseudo-colors of the rectangle-marked area and was obtained after unmixing the individual colors red and blue with spectral imaging. Colocalization of red and blue is indicated in yellow. Spectral imaging analysis of this double-stained series of sections clearly shows the presence of an occasional IL-17pos T cell in psoriatic lesions, whereas IL-22pos T cells were absent. The IL-17 expression in psoriatic skin was predominantly confined to neutrophils and mast cells and IL-22 was highly expressed in many dendritic cells and in most macrophages. The figure is representative of the results from three different donors. Examples of double-stained cells are indicated with an arrow and single-stained cells with an arrowhead. Original magnification 200×.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991333&req=5

pone-0014108-g001: IL-17 and IL-22 expression in psoriatic skin.Microscopic detail of lesional psoriatic skin stained for IL-17 (A–D) or IL-22 (E–H) in combination with CD3 (A, B, E), myeloperoxidase (C), tryptase (D, H), CD11c (F), or CD68 (G). Cytokines are visualized in blue and all different cell markers in red. Each set of three small pictures on the right side represents a composite fluorescent-like image in pseudo-colors of the rectangle-marked area and was obtained after unmixing the individual colors red and blue with spectral imaging. Colocalization of red and blue is indicated in yellow. Spectral imaging analysis of this double-stained series of sections clearly shows the presence of an occasional IL-17pos T cell in psoriatic lesions, whereas IL-22pos T cells were absent. The IL-17 expression in psoriatic skin was predominantly confined to neutrophils and mast cells and IL-22 was highly expressed in many dendritic cells and in most macrophages. The figure is representative of the results from three different donors. Examples of double-stained cells are indicated with an arrow and single-stained cells with an arrowhead. Original magnification 200×.
Mentions: In order to determine the presence and distribution of IL-17 producing T cells in situ, we performed double staining on skin sections from lesional psoriatic skin and healthy normal skin. Spectral digital imaging was used for objective determination of colocalization. Whereas clear IL-17pos and CD3pos cells could be observed in lesional psoriatic skin (Figures 1A and 1B), only an occasional T cell appeared to co-express IL-17. Nevertheless, the presence of IL-17pos T cells seemed to be a specific feature of lesional skin, as in sections from normal skin no double stained cells could be detected (data not shown). In order to identify the IL-17pos non-T cells, we performed additional double stainings. We found that the majority of neutrophils (myeloperoxidase positive) and virtually all mast cells (tryptase positive) in psoriatic skin were IL-17pos (Figures 1C and 1D). We could also detect IL-17pos cells in normal skin, which all appeared to be mast cells and not neutrophils (data not shown).

Bottom Line: Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin.Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin.Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.c.res@amc.uva.nl

ABSTRACT

Background: Although recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ.

Methodology/principal findings: By spectral imaging analysis of double-stained skin sections we demonstrated that IL-17 was mainly expressed by mast cells and neutrophils and IL-22 by macrophages and dendritic cells. Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin. However, examination of in vitro-activated T cells by flow cytometry revealed that substantial percentages of skin-derived CD4 and CD8 T cells were able to produce IL-17A alone or together with IL-22 (i.e. Th17 and Tc17, respectively) or to produce IL-22 in absence of IL-17A and IFN-γ (i.e. Th22 and Tc22, respectively). Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin. Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well.

Conclusions/significance: The increased presence of Tc17 and Tc22 cells in lesional psoriatic skin suggests that these types of CD8 T cells play a significant role in the pathogenesis of psoriasis. As part of the skin-derived IL-17A(pos) CD4 and CD8 T clones developed into IL-22 single-producers, this demonstrates plasticity in their cytokine production profile and suggests a developmental relationship between Th17 and Th22 cells and between Tc17 and Tc22 cells.

Show MeSH
Related in: MedlinePlus